The research proposed has as its long-term objective the delineation of tHe structural pathways and ultrastructural components underlying cell-cell communication in cortical bone repair. Improved understanding of the cellular biology of bone repair is of major importance in the management of orthopaedic conditions as diverse as complex fractures, osteonecrosis of the femoral head, and the repair of large defects left by tumor resections, limb lengthenings, or massive trauma or infection. It is hypothesized that at each stage of repair, cell-cell communication is mediated by intercellular gap junctions and that each osteoblast and osteocyte cell process contains a gap junction by which it relates to the processes of adjacent cells. This will be tested by following cell processes in their entirety from cell to cell in each of the repair cell types (mesenchymal cells, osteoblasts and osteocytes). Additional specific studies relating to cell-cell communication will assess: i) ultrastructural characteristics of gap junctions of bone; ii) immunocytochemistry of intermediate filaments of the cell processes; and iii) the numbers and three-dimensional relationships of the cell processes of the various types of repair cell. Repair is studied in 2.4 millimeter femoral and tibial cortical defects in skeletally mature New Zealand white rabbits. All operations are performed under sterile conditions using general anesthesia. The investigations involve the use of: Light microscopy using plastic embedded toluidine blue stained sections; serial light microscopy sections undergoing three-dimensional reconstruction; polarizing light microscopy; histomorphometry; transmission electron microscopy; serial section transmission electron microscopy; scanning electron microscopy; and immunocytochemistry using immunogold silver staining for the identification of intermediate filaments. The organizational framework of the proposal involves i) the investigation of three structural phenomena: intercellular gap junctions, intermediate filaments, and osteoblast and osteocyte cell process development; ii) in association with three repair cell types: mesenchymal cells, osteoblasts (mesenchymal and surface), and osteocytes; iii) at three time frames: 1 to 7 days, 2 to 8 weeks, and 12-36-52 weeks.